Nejvíce citovaný článek - PubMed ID 12037147
Induction of long-term tolerance to β-cell autoantigens has been investigated both in animal models and in human type 1 diabetes (T1D) in order to prevent the disease. As regards external compounds, the dietary plant protein fraction has been associated with high penetrance of the disease, whereas gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4(+)Foxp3(+) T cells and even more significant induction of γδ T cells in mucosal, but not in non-mucosal lymphoid compartments. This prevention strategy was characterized by an increased proportion of IL-10 and a decreased proportion of IL-2, IL-4 and IFN-γ-positive CD4(+)Foxp3(+) T cells, and IFN-γ-positive γδ T cells, preferentially in mucosal lymphoid organs. In conclusion, i.n. vaccination with gliadin, an environmental antigen with possible etiological influence in T1D, may represent a novel, safer strategy for prevention or even early cure of T1D.
- MeSH
- aplikace intranazální MeSH
- CD4-pozitivní T-lymfocyty imunologie MeSH
- cytokiny metabolismus MeSH
- diabetes mellitus 1. typu farmakoterapie imunologie prevence a kontrola MeSH
- forkhead transkripční faktory metabolismus MeSH
- gliadin aplikace a dávkování terapeutické užití MeSH
- gluteny aplikace a dávkování MeSH
- lidé MeSH
- lymfoidní tkáň imunologie patologie MeSH
- myši inbrední NOD MeSH
- počet lymfocytů MeSH
- slizniční imunita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny MeSH
- forkhead transkripční faktory MeSH
- FOXP3 protein, human MeSH Prohlížeč
- gliadin MeSH
- gluteny MeSH